| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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| Other Sizes |
| Targets |
ErbB2 10 nM (IC50)
CP-724714 selectively targets the HER2/ErbB2 receptor tyrosine kinase. It binds to the intracellular domain of HER2, reversibly inhibiting its tyrosine kinase activity. This inhibition disrupts downstream signaling pathways, including the PI3K/AKT and MAPK pathways, which are critical for tumor cell proliferation and survival. Its high selectivity for HER2 over other kinases makes it a valuable tool for studying HER2-driven cancers. |
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| ln Vitro |
Insulin receptor, insulin-like growth factor-I receptor, platelet-derived growth factor β, vascular endothelial growth factor 2, Abl, Src, c-Met, JNK-2, JNK-3, ZAP-70, Cdk-2, and Cdk-5 are among the receptors for which CP-724714 is >1,000 times less potent[1]. At concentrations as low as 50 nmol/L (IC50=32 nM), CP-724714 potently inhibits the EGF-induced autophosphorylation of the chimera containing the erbB2 kinase domain; however, its potency against EGFR is noticeably lower[1]. In vitro, CP-724714 (1 μM; 24 hours) causes G1 cell cycle block in BT-474 human breast carcinoma cells that overexpress erbB2[1].
In vitro, CP-724714 is a potent inhibitor of HER2 with an IC50 of 10 nM. Its activity is assessed using kinase assays and cell-based proliferation assays in HER2-overexpressing cancer cell lines. It shows high selectivity for HER2, with significantly less activity against EGFR, InsR, PDGFR, VEGFR2, and other kinases. This selectivity profile makes it a useful tool for studying HER2-specific signaling. |
| ln Vivo |
ErbB2 receptor phosphorylation is reduced in a concentration-dependent manner by CP-724714 (3.25-100 mg/kg; po; 0.5-8 hours)[1]. CP-724714 (6.25–100 mg/kg; po; qd; for 8–40 days) suppresses the growth of FRE-erbB2 xenografts[1]. Apoptosis is induced in response to CP-724714 (Athymic, female FRE-erbB2 xenograft-bearing mice; 30 or 100 mg/kg; po) in a time- and dose-dependent manner. This was seen as early as 4 to 8 hours following dosing. Eight hours after dose, over 75% more tumor cells in the 100 mg/kg treatment group showed signs of apoptosis than in the vehicle control group. Regression of BT-474 tumors and considerable suppression of several other human tumor xenografts are induced by CP-724714. Furthermore, CP-724714 had no discernible effects on heart tissue and a positive nonclinical toxicity profile[1].
In vivo, CP-724714 has shown promise in preclinical studies, demonstrating potential therapeutic benefits in cancers such as breast, lung, and head and neck carcinomas. Its orally bioavailable nature supports its use in animal models. The compound's efficacy is evaluated in xenograft models of HER2-overexpressing tumors, where it inhibits tumor growth by blocking HER2-mediated signaling. |
| Enzyme Assay |
Cell-free assays for CP-724714 typically involve measuring its inhibitory activity against HER2 kinase using biochemical kinase assays. The IC50 value of 10 nM is determined by measuring the phosphorylation of a peptide substrate in the presence of varying concentrations of the inhibitor. These assays are used to characterize the compound's potency and selectivity profile against HER2 and a panel of other kinases.
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| Cell Assay |
Cell Cycle Analysis[1]
Cell Types: erbB2-amplified BT-474 breast cancer cells Tested Concentrations: 1 μM Incubation Duration: 24 hrs (hours) Experimental Results: Resulted in accumulation of cells in G1 phase and a marked reduction in S-phase cells. In vitro cellular assays are conducted to evaluate the functional activity of CP-724714. HER2-overexpressing cancer cell lines are treated with the compound. Cell viability and proliferation are measured to assess the compound's anti-proliferative effects. HER2 phosphorylation and downstream signaling events are also measured to confirm inhibition of the target kinase, confirming its ability to block HER2-driven cell growth. |
| Animal Protocol |
Animal/Disease Models: Female athymic mice (bearing FRE-erbB2 xenografts)[1]
Doses: 3.25-100 mg/kg Route of Administration: Po; 0.5-8 hrs (hours) Experimental Results: Produced a reduction of erbB2 tyrosine phosphorylation in FRE-erbB2 xenografts. Animal/Disease Models: Athymic female mice bearing FRE-erbB2 xenografts[1] Doses: 6.25- 100 mg/kg Route of Administration: Po; qd; for 8 to 40 day Experimental Results: Resulted in an inhibition of FRE-erbB2 xenografts. In vivo animal experiments typically involve xenograft models of HER2-driven cancers, such as breast cancer. Mice bearing HER2-overexpressing tumors are administered CP-724714. Tumor growth is monitored over time to assess the compound's efficacy in inhibiting tumor progression. These studies are essential for demonstrating the in vivo antitumor activity of the compound. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of CP-724714 are characteristic of an orally bioavailable small molecule inhibitor. Its molecular weight is 469.54. The compound is designed to have favorable drug-like properties to support oral administration and efficacy in vivo. While detailed PK parameters are not widely published, its oral bioavailability is a key feature for its preclinical development.
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| Toxicity/Toxicokinetics |
The toxicity profile of CP-724714 is not extensively documented but is likely to be similar to other HER2 inhibitors. Common adverse effects associated with HER2-targeted therapies may include diarrhea, fatigue, and cardiotoxicity. Preclinical studies would typically involve acute and chronic dosing in animal models to assess safety margins and identify potential target organ toxicities.
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| References |
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| Additional Infomation |
CP-724714 is a 2-methoxy-N-[3-[4-[3-methyl-4-[(6-methyl-3-pyridyl)oxy]anilino]-6-quinazolino]propyl-2-enyl]acetamide, wherein the double bond is in the trans configuration. It is a potent inhibitor of HER2/ErbB2 (IC50 = 10 nM) and possesses anticancer activity. It can function as an EC 2.7.10.1 (receptor protein tyrosine kinase) inhibitor, an antitumor drug, an apoptosis inducer, and a hepatotoxic agent. CP-724,714 has been used in investigational clinical trials for the treatment of breast cancer, breast tumors, and tumor metastases. The HER2 inhibitor CP-724,714 is a quinazoline compound with high oral bioavailability and potential antitumor activity. CP-724,714 selectively binds to the intracellular domain of HER2, reversibly inhibiting its tyrosine kinase activity, thereby suppressing tumor cell growth. HER2 is a member of the epidermal growth factor receptor (EGFR) family and is overexpressed in many adenocarcinomas, particularly breast cancer. (NCI04)
CP-724714 is a potent and selective HER2/ErbB2 inhibitor with an IC50 of 10 nM and high selectivity over other kinases. It has shown promise in preclinical studies for the treatment of HER2-driven cancers. The compound is used for research purposes to study HER2 biology and the development of targeted cancer therapies. It is not approved for therapeutic use. |
| Molecular Formula |
C27H27N5O3
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|---|---|
| Molecular Weight |
469.53
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| Exact Mass |
469.211
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| CAS # |
383432-38-0
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| Related CAS # |
(E/Z)-CP-724714;537705-08-1
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| PubChem CID |
9874913
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
687.3±55.0 °C at 760 mmHg
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| Flash Point |
369.5±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.663
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| LogP |
4.05
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
35
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| Complexity |
692
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=NC=C(C=C1)OC2=C(C=C(C=C2)NC3=NC=NC4=C3C=C(C=C4)/C=C/CNC(=O)COC)C
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| InChi Key |
LLVZBTWPGQVVLW-SNAWJCMRSA-N
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| InChi Code |
InChI=1S/C27H27N5O3/c1-18-13-21(8-11-25(18)35-22-9-6-19(2)29-15-22)32-27-23-14-20(7-10-24(23)30-17-31-27)5-4-12-28-26(33)16-34-3/h4-11,13-15,17H,12,16H2,1-3H3,(H,28,33)(H,30,31,32)/b5-4+
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| Chemical Name |
2-methoxy-N-[(E)-3-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-6-yl]prop-2-enyl]acetamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ≥ 50 mg/mL (106.49 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1298 mL | 10.6489 mL | 21.2979 mL | |
| 5 mM | 0.4260 mL | 2.1298 mL | 4.2596 mL | |
| 10 mM | 0.2130 mL | 1.0649 mL | 2.1298 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT00055926
Conditions:Breast CancerLink: https://clinicaltrials.gov/ct2/show/NCT00102895
Conditions:Breast Neoplasms|Neoplasm MetastasisProducts are for research use only; We do not sell to patients
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